OVERVIEW

What kind of disease is Sjögren's syndrome?

Sjögren's syndrome (SS) is one of the common rheumatic diseases, primarily affecting exocrine glands such as the lacrimal and salivary glands. It is a chronic autoimmune disease characterized by significant lymphocyte infiltration.

Patients may experience common clinical manifestations such as dry keratoconjunctivitis and xerostomia. The condition can also involve vital internal organs like the lungs, liver, pancreas, and kidneys, and may even affect the nervous system, leading to complex clinical presentations.

Sjögren's syndrome can be classified into primary and secondary types. Primary Sjögren's syndrome occurs independently without another diagnosed connective tissue disease, while secondary Sjögren's syndrome develops in association with another confirmed connective tissue disease, such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, polymyositis, or dermatomyositis.

Currently, there is no cure for Sjögren's syndrome. Treatment mainly involves substitution therapy (e.g., artificial saliva or tears) and symptomatic management. Most patients have a relatively favorable prognosis.

Who is most susceptible to Sjögren's syndrome? What is its prevalence?

Sjögren's syndrome predominantly affects women, particularly those aged 30–60, accounting for about 90% of all cases (i.e., 90 out of 100 patients are women in this age group). However, it can occur at any age, including in children and adolescents. The prevalence in women is significantly higher than in men, approximately 9–10 times greater. In China, the prevalence of primary Sjögren's syndrome is about 0.29%–0.77% (affecting 29–77 people per 10,000 individuals)^[1].

SYMPTOMS

What are the systemic manifestations of Sjögren's syndrome?

Patients with Sjögren's syndrome may experience multi-system involvement, affecting the respiratory, digestive, nervous, hematologic, urinary systems, as well as the skin and musculoskeletal system, leading to corresponding clinical manifestations. Patients may also exhibit systemic symptoms such as fatigue and low-grade fever (axillary temperature above the normal range of 36°C–37°C but not exceeding 38°C). A few cases may present with high fever (axillary temperature rising to 39.1°C–41°C)^[2].

What are the respiratory manifestations of Sjögren's syndrome?

When Sjögren's syndrome affects the respiratory mucosa, it may cause a dry cough (cough with little or no phlegm). Involvement of the small airways can lead to dyspnea (a subjective feeling of insufficient air, labored breathing, or suffocation). If the disease affects the lungs, chest CT (computed tomography) may reveal interstitial lung disease, pulmonary hypertension, pleural effusion, or even diffuse pulmonary fibrosis in some cases. A minority of patients may develop respiratory failure, increasing the risk of death.

What are the digestive manifestations of Sjögren's syndrome?

Involvement of the exocrine glands in the gastrointestinal mucosa may cause symptoms of atrophic gastritis, such as bloating and diarrhea. It may also be associated with gastroesophageal reflux disease, presenting as acid reflux and heartburn. Other nonspecific symptoms include reduced gastric acid and chronic diarrhea.

About 20% of patients may experience liver damage, such as hepatomegaly or abnormal liver function, often coexisting with autoimmune liver diseases like primary biliary cholangitis or autoimmune hepatitis. Additionally, certain medications used to treat Sjögren's syndrome, such as tacrolimus or methotrexate (immunosuppressants), may also cause drug-induced liver injury^[3].

Does Sjögren's syndrome commonly affect the nervous system? What are the manifestations if it does?

Patients with Sjögren's syndrome may develop neurological damage, affecting the central nervous system (CNS) or peripheral nervous system (PNS), with PNS involvement being the most common.

1. Peripheral nervous system: The condition primarily affects sensory nerve fibers, leading to clinical manifestations such as abnormal sensation or motor function, loss of light touch, proprioception, or vibration sense, or weakness (e.g., a glove-like sensation in the hands or unsteady gait)^[4].

2. Central nervous system: The manifestations vary, including hemiplegia, epilepsy, mental or consciousness disorders, and severe cases may involve cognitive impairment (poor memory and concentration). Autonomic dysfunction, such as localized hyperhidrosis or orthostatic hypotension, may also occur.

What are the hematologic manifestations of Sjögren's syndrome?

Patients may develop anemia, with blood tests showing leukopenia or thrombocytopenia. Some may have reductions in two or more blood cell lines, and severe cases may present with bleeding. Lymphoproliferation is common in this disease, usually benign, but a minority may progress to pseudolymphoma or malignant lymphoma. The incidence of malignant lymphoma in these patients is nearly 40 times higher than in the general population^[3].

What are the renal manifestations of Sjögren's syndrome?

Renal involvement in Sjögren's syndrome may lead to increased nocturia (more than twice per night) or nocturnal urine output exceeding daytime output. Patients may experience extreme thirst, excessive water intake, and polyuria (24-hour urine output reaching 5–10 L or more), with reduced urine specific gravity. Some patients may also have lower back pain or hematuria.

What are the cutaneous manifestations of Sjögren's syndrome?

Patients often experience dry skin, which may be severe and accompanied by itching. Allergic purpura-like rashes are also common, typically appearing on the lower limbs as well-defined, millet-sized, non-blanching red papules that occur in batches. Other skin manifestations include urticaria-like rashes and erythema nodosum. Some patients may develop Raynaud's phenomenon (where fingers or toes turn white, then purple, and finally red upon exposure to cold or stress), though it is usually mild and does not lead to digital ulcers or tissue atrophy.

What are the musculoskeletal manifestations of Sjögren's syndrome?

About 70%–80% of patients experience joint pain, but only 10% develop joint swelling, which is usually mild and transient. Erosive arthritis is rare. Approximately 3%–14% of patients may exhibit myositis^[3].

Why are Sjögren's syndrome patients prone to osteoporosis?

The causes of osteoporosis in Sjögren's syndrome are multifactorial:

1. Inflammatory reactions associated with the disease itself can lead to osteoporosis.

2. Renal involvement may disrupt calcium and phosphorus metabolism, contributing to osteoporosis.

3. Long-term use of glucocorticoids (e.g., cortisone) in treatment may also induce osteoporosis^[3].

Why are Sjögren's syndrome patients prone to hyperglobulinemia?

Due to hyperactive humoral immunity, B cells become overactivated and dysfunctional, producing excessive immunoglobulins. Thus, patients are prone to hyperglobulinemia. All three major immunoglobulins (IgG, IgA, IgM) may increase, with IgG being the most prominent.

What does the dry mouth symptom in Sjögren's syndrome refer to?

Dry mouth refers to the need for constant water intake while speaking or eating solid foods. The tongue may appear smooth, cracked, or erythematous.

What is the "rampant caries" symptom in Sjögren's syndrome?

Rampant caries is a characteristic feature of Sjögren's syndrome, where teeth gradually darken, break off in small fragments, and eventually only tooth stumps remain.

Which exocrine glands can Sjögren's syndrome affect?

In addition to the lacrimal glands, Sjögren's syndrome may involve the parotid and/or submandibular glands, causing swelling, pain, and tenderness. About 50% of primary Sjögren's syndrome patients experience salivary gland enlargement, whereas it is less common in secondary cases^[3].

What are the ocular manifestations of Sjögren's syndrome?

Lacrimal gland involvement may cause symptoms such as dryness, foreign body sensation, burning, itching, photophobia, eye redness, blurred vision, fatigue, inability to produce tears when crying, and intolerance to smoky environments.

Why do Sjögren's syndrome patients develop hypokalemia?

When Sjögren's syndrome involves the kidneys, it may damage the distal renal tubules, reducing hydrogen ion secretion and increasing blood hydrogen ion concentration, leading to decreased blood pH. In renal tubular acidosis, excessive potassium excretion in urine lowers blood potassium levels, resulting in hypokalemic paralysis. Patients may experience limb weakness, difficulty sitting up or turning over, and in severe cases, respiratory distress.

Is there a relationship between Sjögren's syndrome and tumors?

Patients with Sjögren's syndrome may develop benign lymphoproliferation, leading to lymphocyte aggregation (pseudolymphoma). If this progresses to malignant proliferation, lymphoma may occur.

Besides lymphoma, patients have an increased risk of multiple myeloma, thymoma, tongue squamous cell carcinoma, parotid mucoepidermoid carcinoma, breast cancer, gastric cancer, and colon cancer. Studies report that the incidence of malignancies in Sjögren's syndrome patients is 1.42–2.5 times higher than in the general population, while the risk of lymphoma is 6–44 times higher^[5].

Why are Sjögren's syndrome patients prone to tumors?

The exact mechanisms remain unclear but may involve genetic susceptibility, chronic viral infections (e.g., EBV), dysregulation of tumor suppressor genes, impaired immune regulation, ectopic germinal center formation (lymphoid tissue developing in non-lymphoid organs), and long-term immunosuppressant use.

CAUSES

What causes Sjögren's syndrome?

The exact cause of Sjögren's syndrome is not fully understood, but it may be related to a combination of factors such as infections, genetic predisposition, immune dysfunction, and sex hormones ^[3].

Under the combined influence of these factors, the body's cellular and humoral immunity becomes hyperactive, producing large amounts of cytokines, immunoglobulins, and various autoantibodies, leading to inflammatory damage in local tissues.

What are the possible warning signs of lymphoma in Sjögren's syndrome?

When Sjögren's syndrome patients exhibit symptoms such as significantly enlarged lymph nodes, salivary or submandibular glands with hardened texture, a shift from polyclonal to monoclonal immunoglobulin proliferation, disappearance of autoantibodies, weight loss, or fever, these may indicate a transition from benign to malignant disease.

Which medications can cause dry symptoms?

Certain medications can induce dry symptoms clinically, including α-blockers (e.g., phentolamine mesylate), β-blockers (e.g., atenolol), antidepressants (e.g., fluoxetine), methocarbamol, oxybutynin, bethanechol, levodopa, pseudoephedrine, chlorpheniramine, and anticholinergic drugs (e.g., atropine).

Therefore, when patients present with dry symptoms, they should inform their doctors of their detailed medication history to rule out drug-induced causes.

Is Sjögren's syndrome hereditary?

There is a certain genetic risk. The onset of Sjögren's syndrome is associated with genetic factors, and relatives of affected individuals are more likely to develop the condition compared to the general population ^[1].

Thus, family members should be aware of its basic symptoms (e.g., dry mouth, dry skin) and seek prompt medical attention if such manifestations occur to avoid delays in diagnosis and treatment.

DIAGNOSIS

Is dry mouth necessarily caused by Sjögren's syndrome?

Not necessarily.

Dry mouth is a common symptom of Sjögren's syndrome, but some patients may not experience it and may instead present with arthritis, urinary tract infections, or other initial symptoms.

Conditions such as lymphoma, amyloidosis, sarcoidosis, hepatitis C, AIDS, uncontrolled diabetes, graft-versus-host disease, and long-term use of antidepressants, anticholinergic drugs, or sedatives can also cause dry mouth. Therefore, dry mouth is not always due to Sjögren's syndrome, and these factors must be ruled out during diagnosis.

Is dry eye disease in Sjögren's syndrome the same as common dry eye disease?

No.

Dry eye disease: A common ophthalmological condition caused by multiple factors affecting tears and the ocular surface. It leads to discomfort, visual disturbances, unstable tear film, potential damage to ocular surface tissues, increased tear film osmolarity, and ocular surface inflammation.

Sjögren's syndrome-related dry eye disease: Less common. While Sjögren's syndrome often presents with dry eye symptoms similar to dry eye disease, not all patients diagnosed with dry eye disease have Sjögren's syndrome.

What is the Schirmer test for Sjögren's syndrome?

A doctor places two filter paper strips under the lower eyelids of the patient, who then closes their eyes for 5 minutes. The length of the strips wetted by tears is measured. A positive result for Sjögren's syndrome is ≤ 5 mm/5 min ^[1].

What is tear film breakup time in Sjögren's syndrome testing?

Tear film breakup time refers to the duration before the tear film ruptures without blinking. The test involves the patient blinking and then keeping their eyes open while the doctor observes and records the time until the first dry spot appears on the tear film.

In healthy individuals, the tear film is stable and typically ruptures after 10 seconds. A breakup time ≤ 10 seconds is considered abnormal ^[1].

What is corneal staining in Sjögren's syndrome testing?

When corneal damage occurs, a dye (fluorescein sodium) causes dead cells to fluoresce brightly under cobalt blue light. The doctor scores the damage based on the number and distribution of high-fluorescence spots.

How is Sjögren's syndrome diagnosed?

Doctors diagnose it by reviewing medication history, conducting physical exams (including systemic evaluation), and performing lab tests (e.g., serum anti-SSA/SSB antibodies) and auxiliary tests (e.g., Schirmer test, salivary gland imaging). Two main diagnostic criteria exist, but the 2002 revised International Classification Criteria for Primary Sjögren's Syndrome is more commonly used due to subjective flaws in the European criteria.

European Diagnostic Criteria for Sjögren's Syndrome:

1. Persistent dry eyes for ≥ 3 months, gritty sensation, or using artificial tears ≥ 3 times daily (any one qualifies).
2. Persistent dry mouth for ≥ 3 months, needing liquids to swallow dry food, or recurrent/persistent parotid swelling (any one qualifies).
3. Schirmer test ≤ 5 mm/min or corneal staining score ≥ 4.
4. Lip biopsy showing ≥ 1 lymphocyte focus/4 mm².
5. Positive parotid sialography, salivary scintigraphy, or salivary flow rate.
6. Serum anti-SSA/SSB antibodies positive.

Meeting ≥ 4 of the 6 criteria confirms primary Sjögren's syndrome. If another connective tissue disease is present with criteria 1 or 2 plus 2 of 3, 4, or 5, secondary Sjögren's syndrome is diagnosed ^[6].
(Diagnosis must be made by a specialist.)

2002 Revised International Classification Criteria for Primary Sjögren's Syndrome:

1. Oral symptoms (≥ 1 of 3):
   • Daily dry mouth for ≥ 3 months;
   • Recurrent/persistent parotid swelling in adulthood;
   • Needing liquids to swallow dry food.
2. Ocular symptoms (≥ 1 of 3):
   • Daily intolerable dry eyes for ≥ 3 months;
   • Recurrent gritty sensation;
   • Using artificial tears ≥ 3 times daily.
3. Ocular signs (≥ 1 positive):
   • Schirmer test ≤ 5 mm/5 min;
   • Corneal staining ≥ 4 (van Bijsterveld score).
4. Histopathology: Lip biopsy showing ≥ 1 lymphocyte focus (≥ 50 cells/4 mm²).
5. Salivary gland involvement (≥ 1 positive):
   • Salivary flow rate ≤ 1.5 ml/15 min;
   • Positive parotid sialography;
   • Positive salivary scintigraphy.
6. Autoantibodies: Anti-SSA or anti-SSB positive (double immunodiffusion).

Classification:

1. Primary Sjögren's syndrome (no underlying disease):
   • Meet ≥ 4 criteria, including IV (histopathology) and/or VI (autoantibodies); OR
   • Meet any 3 of III, IV, V, and VI.
2. Secondary Sjögren's syndrome (with underlying connective tissue disease): Meet I or II plus any 2 of III, IV, and V.

Exclude: Head/neck radiation, hepatitis C, AIDS, lymphoma, sarcoidosis, graft-versus-host disease, or anticholinergic drug use (e.g., atropine, scopolamine) ^[3].

TREATMENT

Which department should I visit for Sjogren's syndrome?

The first choice is the rheumatology and immunology department. If this department is not available, you can go to general internal medicine or other departments. If symptoms like dry mouth and dry eyes are severe, you may also need comprehensive diagnosis and treatment from departments such as dentistry and ophthalmology.

How is Sjogren's syndrome treated?

There is currently no cure for Sjogren's syndrome, but symptoms can be alleviated through treatment. For patients without organ damage, replacement therapy (supplementing deficient substances) and symptomatic treatment are the main approaches. Patients with organ damage require immunosuppressive therapy ^[1,3].

1. Local treatment: Stop smoking, drinking, and avoid medications that cause dry mouth, such as atropine and amitriptyline. Maintain oral hygiene, rinse frequently, and reduce the risk of cavities and secondary infections. Substitutes like artificial tears and saliva can alleviate local symptoms.

2. Systemic treatment: For patients with arthritis, pulmonary interstitial changes, liver or kidney involvement, or neurological symptoms, glucocorticoids (e.g., cortisone) and disease-modifying antirheumatic drugs (e.g., tacrolimus, methotrexate) may be prescribed.

3. Symptomatic management: Hypokalemic periodic paralysis is primarily treated with intravenous potassium, followed by oral potassium supplements—some patients may require lifelong use. NSAIDs can help relieve muscle and joint pain. Patients with malignant lymphoma should undergo prompt combination chemotherapy.

4. Biological agents: Anti-CD20 monoclonal antibodies can inhibit B-cell production. While biologics are widely used clinically, there is no confirmed indication for primary Sjogren's syndrome.

5. Removing triggers: Eradicating Helicobacter pylori can prevent and treat gastric lesions caused by Sjogren's syndrome and may even alleviate other symptoms.

How to treat dry mouth caused by Sjogren's syndrome?

1. Alleviate dry mouth: Quit smoking and drinking, avoid medications that cause dry mouth (e.g., atropine, amitriptyline). Maintain oral hygiene, use fluoride toothpaste or mouthwash, and schedule regular dental checkups.

2. Substitute therapy: Drink water or rinse frequently. Artificial saliva can be used if necessary. A humidifier can increase air moisture and help relieve symptoms.

3. Stimulate salivary secretion: Chewing sugar-free gum may help stimulate saliva production.

How to treat dry eye disease in Sjogren's syndrome?

Dry eye disease in Sjogren's syndrome is difficult to cure, but treatment aims to maximize symptom relief and reduce corneal and conjunctival damage. The most basic treatment is artificial tears. Topical corticosteroids or immunosuppressants (e.g., cyclosporine eye drops, sodium hyaluronate eye drops) may also be effective ^[1].

What is the prognosis for Sjogren's syndrome?

Most patients with Sjogren's syndrome have a good prognosis. Those with mild symptoms (limited to dry mouth and eyes) can lead normal lives and work, with a life expectancy similar to the general population. Patients with organ damage can usually control or achieve remission with appropriate treatment, though relapses are common. Severe organ damage leads to a poor prognosis ^[3].

The main causes of death include pulmonary fibrosis with infection, pulmonary hypertension, kidney failure, lymphoma, and central nervous system disorders.

DIET & LIFESTYLE

What should patients with Sjögren's syndrome pay attention to in their diet and daily life?

• Diet: Patients with Sjögren's syndrome may find it difficult to eat dry foods, so they should consume more liquid-based foods such as rice porridge or steamed egg custard. Avoid spicy, fried, overly salty, or sour foods. Increase intake of vegetables and fruits like loofah, celery, daylily, lotus root, and yam, which can help stimulate saliva production and maintain oral moisture.

• Oral care: Prevent bacterial growth in the mouth by brushing teeth twice daily (morning and night) and rinsing after meals. Avoid smoking and alcohol, and minimize exposure to irritants like dust. If cavities are present, seek prompt dental treatment. Stay hydrated to maintain oral moisture.

• Medication: Avoid drugs that may cause dry mouth to alleviate symptoms. Examples include α-blockers (e.g., phentolamine mesylate), β-blockers (e.g., atenolol), antidepressants (e.g., fluoxetine), methocarbamol, oxybutynin, bethanechol, levodopa, pseudoephedrine, chlorpheniramine, and anticholinergics (e.g., atropine).

PREVENTION

Can Sjögren's Syndrome Be Prevented?

No. Currently, there are no definitive preventive measures.

Since it is associated with genetic, infectious, immune, and other factors, and its exact pathogenesis remains unclear, targeted prevention methods are lacking.

Healthy individuals should maintain a healthy lifestyle: avoid smoking; exercise regularly and avoid prolonged sitting (more than 60 minutes), prevent overweight and obesity, engage in physical activity 3–5 times per week for about 30 minutes each session, combining aerobic exercises (e.g., jogging, cycling) with strength training (e.g., pull-ups, squats) at moderate intensity without overexertion; learn to manage stress and emotional tension.

Patients with Sjögren's Syndrome who plan to have children may seek genetic counseling at relevant institutions to assess the risk of the disease in their offspring.